バルデコキシブ
バルデコキシブ · 4-(5-メチル-3-フェニル-4-イソオキサゾリル)ベンゼンスルホンアミド · 4-(5-メチル-3-フェニル-1,2-オキサゾール-4-イル)ベンゼン-1-スルホンアミド · 3-フェニル-4-(4-スルファモイルフェニル)-5-メチルイソオキサゾール · 4-(3-フェニル-5-メチル-4-イソオキサゾリル)ベンゼンスルホンアミド · 4-[3-フェニル-5-メチルイソオキサゾール-4-イル]ベンゼンスルホンアミド · 4-(3-フェニル-5-メチルイソオキサゾール-4-イル)ベンゼンスルホンアミド · BEXTRA
識別子と物理属性
| CAS No. | 181695-72-7 |
|---|---|
| 分子式 | C16H14N2O3S |
| 平均分子量 | 314.4 g/mol |
| 単同位体質量 | 314.07251331 g/mol |
| SMILES | Cc1onc(-c2ccccc2)c1-c1ccc(S(N)(=O)=O)cc1 |
| InChIKey | LNPDTQAFDNKSHK-UHFFFAOYSA-N |
| PubChem CID | 119607 |
| ChEMBL | CHEMBL865 |
| ChEBI | CHEBI:63634 |
| EC No. | 448-010-8 |
| DTXSID | DTXSID6044226 |
| 現地名 | バルデコキシブ |
化学・物理的性質
| XLogP | 2.6 |
|---|---|
| 極性表面積 | 94.6 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 5 |
| 回転可能結合数 | 3 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 462 |
| 医薬品 | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | log Kow = 2.67 /Estimated/ |
| Color/Form | White crystalline powder |
| 溶解度 | Soluble in methanol and ethanolfreely soluble in organic solvents and alkaline (pH=12) aqueous solutionRelatively insoluble in water (10 ug/mL) at 25 °C and pH 7>47.2 [ug/mL] (The mean of the results at pH 7.4)DMSO：>25mg/mL |
| Human Drugs | Breast FeedingLactationMilk, HumanAnalgesic AgentsAnti-inflammatory Agents, NonsteroidalFDA approved drugs -> Active ingredientPharmaceuticals |
| 融点 | 160 - 162 °C162-164°C |
| 蒸気圧 | 4.6X10-10 mm Hg at 25 °C /Estimated/ |
| ヘンリー定数 | Henry's Law constant = 2.2X10-11 atm-cu m/mol at 25 °C /Estimated/ |
| Physical Description | Solid |
| Other Experimental Properties | Hydroxyl radical reaction rate constant = 1.3X10-11 cu cm/molec-sec at 25 °C /Estimated/ |
| 沸点 | 481.2±55.0 °C(Predicted) |
| 密度 | 1.303±0.06 g/cm3(Predicted) |
| 貯蔵条件 | room temp |
| pKa（酸解離定数） | 9.83±0.10(Predicted) |
| 外観・状態 | 粉 |
| 色 | ホワイトからオフホワイト |
| ヘンリー定数 | 4.5×105 mol/(m3Pa) at 25℃, HSDB (2015) |
| InChI | InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20) |
| InChIKey | LNPDTQAFDNKSHK-UHFFFAOYSA-N |
| SMILES | C1(S(N)(=O)=O)=CC=C(C2=C(C)ON=C2C2=CC=CC=C2)C=C1 |
| CAS データベース | 181695-72-7(CAS DataBase Reference) |
化学的特性
Valdecoxib is a white crystalline powder that is relatively insoluble in water (10 μg/mL) at 25°C and pH 7.0, soluble in methanol and ethanol, and freely soluble in organic solvents and alkaline (pH=12) aqueous solutions.
安全性と法規制
| GHS 分類 | WarningH361 (97.4%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]P203, P260, P273, P280, P318, P319, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity] |
|---|---|
| 規制情報 | Status: Active Update: 20-08-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/17744 |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl valdecoxib, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Special Reports | Chavez ML, DeKorte CJValdecoxib: A ReviewClin Ther 25 (3): 817-51(2003) |
| Hazard Classes and Categories | Repr. 2 (100%)Repr. 2 (97.4%) |
| 処分方法 | SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations. |
| 相互作用 | Valdecoxib produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alonetherefore, monitoring of lithium concentrations for signs of lithium toxicity is recommended during concurrent usehowever, lithium has no effect on valdecoxib pharmacokinetics.In clinical trials, concurrent use administration of valdecoxib 20 mg with multiple dose of ketoconazole and fluconazole produced increased plasma exposure of valdecoxib by 62% when coadministered with fluconazole and 38% when coadministered with ketoconazole, the increase in plasma concentration of valdecoxib was due to the inhibition of valdecoxib metabolism via p450 2C9 and 3A4 by fluconazole and ketoconazole. |
用途
用途
シクロオキシゲナーゼ2 （COX-2）選択的阻害剤です。抗炎症・鎮痛 作用を示します。重症皮膚反応の危険性が高 く、また、心血管系のリスクが高いと報告さ れています。
用途
COX-2 の強力で選択的な阻害剤です。in vivo で強力な抗炎症作用を示します。
説明
Valdecoxib is a second-generation COX-2 inhibitor, developed as a follow-up to celecoxib for the oral once-daily treatment of osteoarthritis, adult rheumatoid arthritis and menstrual pain. Valdecoxib is approximately 28,000-fold more selective against human recombinant COX-2 than human recombinant COX-1. In an ex viva human whole blood assay, the I&O values against COX-2 and COX-1 were respectively 0.89 PM and 25.4 FM. In animal models, valdecoxib possesses excellent oral activity as an antiinflammatory. In rats, valdecoxib potently inhibited carrageenan footpad edema and adjuvant-induced arthritis.
使用
Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic properties in animal models. It is a potent and selective inhibitor of prostaglandin synthesis primarily through inhibition of COX-2. Valdecoxib is used to relieve some symptoms caused by arthritis (rheumatism), such as inflammation, swelling, stiffness, and joint pain.
一般的な説明
Valdecoxib (VCX) is a diaryl substituted isoxazole compound. It comprises of sulfonyl propanamide and is a metabolite of parecoxib.
製法・合成法
製造方法
The step for the synthesis of valdecoxib: Deoxybenzoin is converted to the corresponding oxime by treatment with hydroxylamine under basic conditions with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. The treatment of the oxime under nitrogen with two equivalents of butyllithium in tetrahydrofuran is followed by cyclization in ethyl acetate or acetic anhydride to the isoxazoline derivative. Finally, treatment of the isoxazoline with cold chlorosulfuric acid followed by reaction of the intermediate with aqueous ammonia afforded valdecoxib.